This project examines in detail the sites of binding of two important carcinogens, 1-methyl-1-nitrosourea (MNU) and 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) to pancreatic tissue. Emphasis is placed on modification of components of the cell nucleus, both DNA and proteins (histones and non-histones). Both of the above compounds can react with macromolecules by two chemical routes, namely alkylation (MNU and MNNG) and carbamoylation (MNU) or guanidination (MNNG), so that a total of four chemical processes are to be examined. Results to date in a model system using L1210 cells in suspension culture indicate that both compounds modify histones and non-histones. The guanidination of histones by MNNG is quantitatively the most important. Histones H1, H2b and H3 are primary targets while H4 is less modified. Non-histones also undergo modification. In guinea pigs both MNU and MNNG show relatively low uptake in pancreas and stomach compared to liver, kidney and small intestine following intraperitoneal injection. However, there is a high concentration of the carcinogens in nuclei of pancreas and stomach relative to the other organs. The significance of these reactions in modifying living tissue in the GI tract, especially the pancreas, in the guinea pig, is currently under investigation. The purpose of the study is to define reactions of significance in the production of pancreatic cancer.